On April 17, 2023, the FDA approved omidubicel-onlv (Omisirge; Gamida Cell), a substantially modified allogeneic cord blood–based cell therapy, to quicken the recovery of neutrophils in the body and reduce the risk for infection in adults and pediatric patients aged ≥12 years with hematologic malignancies who have a planned umbilical cord blood transplant after a myeloablative conditioning regimen, such as radiation or chemotherapy. The FDA granted this approval priority review and breakthrough and orphan drug designations.
“The approval of Omisirge is a significant development in hematopoietic stem cell transplantation,” said Steven M. Devine, MD, Chief Medical Officer, National Marrow Donor Program/Be The Match. “Adding Omisirge as a new donor source may help increase access to stem-cell transplant for patients from racially or ethnically diverse backgrounds who struggle to find a fully matched donor in the registry.”
The approval was based on data from the P0501 study, an open-label, multicenter, international, randomized, phase 3 clinical trial of 125 patients aged 12 to 65 years with hematologic malignancies who received omidubicel or standard unmanipulated cord blood (UCB) unit transplantation after myeloablative conditioning and prophylaxis with a calcineurin inhibitor and mycophenolate mofetil (CellCept) for graft-versus-host disease (GVHD).
In all, 62 of the study participants were randomized to receive omidubicel and 63 were randomized to receive UCB. A total of 52 patients in the omidubicel arm were transplanted and received a median CD34+ cell dose of 9.0 × 106 cells/kg (range, 2.1-47.6 × 106 cells/kg). A total of 56 patients in the UCB arm were transplanted with 1 or 2 cord units (66% received 2 cord units). In the 42 patients with reported postthaw cell dose, the median CD34+ cell dose was 0.2 × 106 cells/kg (range, 0.0-0.8 × 106 cells/kg). Total body irradiation–based and chemotherapy-based regimens were among the many conditioning regimens used in the study.
The major efficacy measures included time to neutrophil recovery after transplant and the incidence of grade 2 or 3 bacterial infections or grade 3 fungal infections through 100 days after transplant. The median time to neutrophil recovery was 12 days in the omidubicel arm (95% confidence interval [CI], 10-15 days) and 22 days in the UCB arm (95% CI, 19-25 days). In the omidubicel and UCB arms, 87% and 83% of patients, respectively, achieved neutrophil recovery. The incidence of grade 2 or 3 bacterial infections or grade 3 fungal infections through 100 days after transplant was 39% in the omidubicel arm and 60% in the UCB arm.
The prescribing information for omidubicel has a boxed warning for fatal or life-threatening infusion reactions, GVHD, engraftment syndrome, and graft failure. In 117 study participants who received omidubicel for the treatment of any disease, 47% had infusion reactions, 58% had acute GVHD, 35% had chronic GVHD, and 3% had graft failure.
The most common grade 3 to 5 adverse reactions in patients with hematologic malignancies were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).